Acidity of carbon acids

In the discussion of the relative acidity of carboxylic acids in Chapter 1, the thermodynamic acidity, expressed as the acid dissociation constant, was taken as the measure of acidity. It is straightforward to determine dissociation constants of such adds in aqueous solution by measurement of the titration curve with a pH-sensitive electrode (pH meter). Determination of the acidity of carbon acids is more difficult. Because most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. Any strong base will deprotonate the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, tetrahydrofuran (THF), and dimethoxyethane (DME) are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as DMSO and cyclohexylamine are used in the preparation of strongly basic carbanions. The high polarity and cation-solvating ability of DMSO facilitate dissociation... 

Studies of gas-phase acidities of carbon acids have appeared in the last ten years, including work on sulfones and sulfoxides189. The acidity of substituted methanes increases in the order... 

The bottom portion of Table 8.1 consists of very weak acids pK. above 17). In most of these acids, the proton is lost from a carbon atom, and such acids are known as carbon acids. The pa s values for such weak acids are often difficult to measure and are known only approximately. The methods used to determine the relative positions of these acids are discussed in Chapter 5. The acidity of carbon acids is proportional to the stability of the carbanions that are their conjugate bases (see p. 227). 

Table 6-18 Acidities of Carbon Acids Relative to Methane ... 

The next issue that arises from the weak acidity of carbon acids involves the degree of self-dissociation. In Eq. 3, the equihbrium constant is determined by measuring the concentration of the four species in the equation, but this requires that the carbon acid self-dissociates to an extent that a measurable quantity of the carbanion is formed. Again, because carbon acids are generally weak, this requirement often is not met and therefore another type of equilibrium measurement... 

Recent developments include the measurement of the kinetic basicities of EGB s by convenient electroanalytical methods. The establishment of a scale of EGB basicities will in turn facilitate the measurement of kinetic acidities of carbon acids. 

For reviews of methods used to measure the acidity of carbon acids, see Jones Q. Rev., Chem. Soc. 1971, 25, 365-378 Fischer Rcwicki Prog. Org. Chem. 1968, 7, 116-161 Reutov Beletskaya Butin. Ref. 11. Chapter I an earlier version of this chapter appeared in Russ. Chem. Rev. 1974, 43. 17-31) Ref. 6. For reviews on acidities of carbon acids, see Gau Assadourian Veracini Prog. Phys. Org. Chem. 1987, 16, 237-285 in Bunccl Durst Comprehensive Carbanion Chemistry, pt. A Elsevier New York, 1980, the reviews by Pcllcritc Brauman. pp. 55-96 (gas phase acidities) and Streitwicscr Juaristi Nebenzahl, pp. 323-381. 

Table 3.10 Acidities of Carbon Acids Containing Electron-Withdrawing Groups...

We have presented evidence that pyrrole-2-carboxylic acid decarboxylates in acid via the addition of water to the carboxyl group, rather than by direct formation of C02.73 This leads to the formation of the conjugate acid of carbonic acid, C(OH)3+, which rapidly dissociates into protonated water and carbon dioxide (Scheme 9). The pKA for protonation of the a-carbon acid of pyrrole is —3.8.74 Although this mechanism of decarboxylation is more complex than the typical dissociative mechanism generating carbon dioxide, the weak carbanion formed will be a poor nucleophile and will not be subject to internal return. However, this leads to a point of interest, in that an enzyme catalyzes the decarboxylation and carboxylation of pyrrole-2-carboxylic acid and pyrrole respectively.75 In the decarboxylation reaction, unlike the case of 2-ketoacids, the enzyme cannot access the potential catalysis available from preventing the internal return from a highly basic carbanion, which could be the reason that the rates of decarboxylation are more comparable to those in solution. Therefore, the enzyme cannot achieve further acceleration of decarboxylation. In the carboxylation of pyrrole, the absence of a reactive carbanion will also make the reaction more difficult however, in this case it occurs more readily than with other aromatic acid decarboxylases. 

The acidities of carbon acids have been extensively discussed before, especially by Cram5 who has constructed a scale of pK values based on the work of Mc-Ewan, Streitwieser, Applequist, and Dessy and known as the MSAD scale. Table 3 shows a selection of these pK values, and also values given by Reutov and co-workers6 derived from polarographic measurements. It is clear from the values shown in Table 3 that substituents such as a-phenyl, a-benzyl, and a-carbethoxy increase the extent of carbanion formation from carbon acids very considerably,... 

Lahti, M. Kankaanpera, A. Virtanen, P. Kinetic acidity of carbon acids the hydroxide ion catalyzed ionization of chloroform and acetophenone in aqueous HMPA. /. Chem. 

Bordwell, F. G. Matthews, W. S. Vanier, N. R. Acidities of carbon acids. IV. Kinetic vs equilibrium acidities as measures of carbanion stabilities. The relative effects of phenylthio, diphe-nylphosphino, and phenyl groups./. Am. Chem. Soc. 1975, 97, 442-443. 

Equilibrium Acidities of Carbon Acids in Dimethyl Sulphoxide6... 

American 243, 148 (1980) Chemische Reaktionen ohne Ldsungsmittel, Spektrmn der Wissenschaft, January 1981, p. 27ff. [116] R. W. Taft Protonic Acidities and Basicities in the Gas Phase and in Solution Substituent and Solvent Effects, Progr. Phys. Org. Chem. 14, 247 (1983). [117] C. R. Moylan and J. 1. Brauman Gas-Phase Acid-Base Chemistry, Annu. Rev. Phys. Chem. 34, 187 (1983). [118] P. Kebarle Ion Thermochemistry and Solvation from Gas-Phase Ion Equilibrium, Annu. Rev. Phys. Chem. 28, 445 (1977). [119] D. K. Bohme, E. Lee-Ruff, and L. B. Young, J. Am. Chem. Soc. 94, 5153 (1972) D. K. Bohme in P. Ausloos (ed.) Interactions between Ions and Molecules, Plenum, New York, 1974, p. 489ff. [120] M. J. Pellerite and J. I. Brauman Gas-Phase Acidities of Carbon Acids, in E. Buncel and T. Durst (eds.) Comprehensive Carbanion Chemistry, Part A, p. 55ff., Elsevier, Amsterdam, 1980. 

The problems involved in the measurement of acidities or relative acidities of weak acids are illustrated by the widely different estimates which have been given for the acidity of substituted acetylenes. Two different approaches have been used for measuring the equilibrium acidity of carbon acids which do not ionize in the pH range. In one approach, the ionization of a carbon acid is studied in mixed solvents containing base. Some of these solutions are more basic than aqueous solutions and by varying the solvent mixture the ionization of acids with pK values in the range 12—25 can be studied. Values at the low end of the pK range are directly compared with aqueous p/iC values. It is assumed that ratios of the activity coefficients (f) for the ionized (S-) and unionized acids (SH) are the same for all the acids studied and an acidity function (86)... 

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